title: Pathogenicity of pandemic H1N1 influenza A virus in immunocompromised cynomolgus macaques.
abstract: Pandemic (H1N1) 2009 influenza virus spread throughout the world since most people did not have immunity against the virus. In the post pandemic phase when many humans might possess immunity against the pandemic virus, one of the concerns is infection in immunocompromised people. Therefore, we used an immunosuppressed macaque model to examine pathogenicity of the pandemic (H1N1) 2009 virus under an immunocompromised condition. The virus in nasal samples of immunosuppressed macaques infected with the pandemic (H1N1) 2009 virus was detected longer after infection than was the virus in nasal samples of immunocompetent macaques. As expected, not only virus amounts but also virus propagation sites in the immunosuppressed macaques were larger than those in lungs of the immunocompetent macaques when they were infected with the pandemic virus. Immunosuppressed macaques possessed low levels of immune cells producing cytokines and chemokines, but levels of inflammatory cytokines/chemokine interleukin (IL)-6, IL-18, and monocyte chemotactic protein (MCP)-1 in lungs of the immunosuppressed macaques were higher than those in lungs of the immunocompetent macaques, though the differences were not statistically significant. Therefore, under an immunosuppressive condition, the pandemic influenza (H1N1) 2009 virus might cause more severe morbidity with high cytokine/chemokine production by the host innate immune system than that seen in macaques under the immunocompetent condition.
authors.affiliation: Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Van Loi
authors.initials: VL
authors.lastname: Pham
authors.forename: Misako
authors.initials: M
authors.lastname: Nakayama
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Itoh
authors.forename: Hirohito
authors.initials: H
authors.lastname: Ishigaki
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Kitano
authors.forename: Masahiko
authors.initials: M
authors.lastname: Arikata
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ishida
authors.forename: Naoko
authors.initials: N
authors.lastname: Kitagawa
authors.forename: Shintaro
authors.initials: S
authors.lastname: Shichinohe
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Okamatsu
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakoda
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Ogasawara
mesh_terms: D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D016867:Immunocompromised Host / Q000276:immunology*; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy / Q000379:methods; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity*; D008168:Lung / Q000276:immunology; D008252:Macaca fascicularis; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication / Q000502:physiology
chemical_list: D016207:Cytokines; D016572:Cyclosporine; D003520:Cyclophosphamide